Interferon-γ-dependent expression of inducible nitric oxide synthase, interleukin-12, and interferon-γ-inducing factor in macrophages elicited by allografted tumor cells

We have examined the mechanisms of activation of macrophages (M∅s) induced by i.p. allografted Meth A tumor cells (Meth A-M∅s) during the rejection of the cells by C57BL/6 mice. Inducible nitric oxide (NO) synthase (iNOS), interleukin-12 (IL-12), and interferon-γ (IFN-γ)-inducing factor (IGIF) were transiently expressed in Meth A-M∅s during the rejection. The expression was impaired in mice in which the gene encoding IFN-γ had been disrupted (IFN-γ -/-). In vitro studies showed that Meth A-M∅s from IFN-γ +/+ mice induced an apoptotic type of cell death in P815 cells, without cell-to-cell contact, in an NO-dependent manner, whereas Meth A-M∅s from IFN-γ -/- mice could not lyse these cells. The iNOS, IL-12, and IGIF expression was also impaired in bacteria-activated M∅s from IFN-γ -/- mice, indicating that IFN-γ, but not IGIF, would be the initial signal that leads to the activation of M∅s in vivo.